Intravenous Thrombolysis in Patients With Ischemic Stroke and Recent Ingestion of Direct Oral Anticoagulants
Authors: Thomas R. Meinel, Duncan Wilson, Henrik Gensicke, Jan F. Scheitz, Peter Ringleb, Ioana Goganau, Johannes Kaesmacher, Hee-Joon Bae, Do Yeon Kim, Pawel Kermer, Kentaro Suzuki, Kazumi Kimura, Kosmas Macha, Masatoshi Koga, Shinichi Wada, Valerian Altersberger, Alexander Salerno, Logesh Palanikumar, Andrea Zini, Stefano Forlivesi, Lars Kellert, Johannes Wischmann, Espen S. Kristoffersen, James Beharry, P. Alan Barber, Jae Beom Hong, Carlo Cereda, Eckhard Schlemm, Yusuke Yakushiji, Sven Poli, Ronen Leker, Michele Romoli, Marialuisa Zedde, Sami Curtze, Benno Ikenberg, Timo Uphaus, David Giannandrea, Pere Cardona Portela, Roland Veltkamp, Annemarei Ranta, Marcel Arnold, Urs Fischer, Jae-Kwan Cha, Teddy Y. Wu, Jan C. Purrucker, David J. Seiffge, Martina Goeldlin, Bernhard Siepen, Madlaine Mueller, Morin Beyeler, Adrian Scutelnic, Simon Jung, Adnan Mujanovic, Christoph Kurmann, Tomas Dobrocky, Eike Piechoviak, Roland Wiest, Arsany Hakim, Philipp Bücke, Zarzitzky Jana, Lichti Carmen, Dmytrow Diana Isabella, João Nuno Ramos, Davide Strambo, Menuela Buehrer, Naaem Simaan, Asaf Honig, Andrei Filioglo, Ilaria Grisendi, Laura Ferri, Maria Claudia Trapasso, Matteo Benini, Rosario Pascarella, Claudio Moratti, Manuela Napoli, Sheetal Sumaria, Klaus Gröschel, Marianne Hahn, Alexandros Polymeris, Christopher Traenka, Annaelle Zietz, Philippe Lyrer, Gian Marco DeMarchis, Sebastian Thilemann, Ines Piot, Lukas Enz, Nils Peters, Mira Katan, Alexander Brehm, Marios Psychogios, Ulrike Prange, Neil Spratt, Laurent Roten, BL Alvin Chew, Jakub Stefela, Regina von Rennenberg, Simon Litmeier, Christoph Riegler, Markus Klammer, Hebun Erdur, Hellwig Simon, Magoni Mauro, Longoni Marco, Cordici Francesco, Biguzzi Sara, Peter Tan, Marko Ercegovac, Ivana Berisavac, David Haupenthal, Luise Gassmann, Armin Marsch, Gabriela Siedler, Louise Weir, Lauren Pesavento, Nawaf Yassi, Stephen Davis, Bonaventure Ip, Thomas Leung, Alexandra Gomez-Exposito, Joshua Mbroh, Johannes Tünnerhoff, Gabriel Barbu, Yi Wang, Annerose Mengel, Feil Katharina, Markus Kowarik, Ulf Ziemann, Jun Yup Kim, Jihoon Kang, Moon-Ku Han, Beom Joon Kim, Kang-Ho Choi, Man-Seok Park, Ki-Hyun Cho, Joon-Tae Kim, Dong-Ick Shin, Kyu Sun Yum, Dae-Hyun Kim, Jae-Kwan Cha, Jong-Moo Park, Kyusik Kang, Yong Soo Kim, Jae Guk Kim, Soo Joo Lee, Mi-Sun Oh, Byung-Chul Lee, Minwoo Lee, Kyung-Ho Yu, Hong-Kyun Park, Keun-Sik Hong, Yong-Jin Cho, Jay Chol Choi, Joong-Goo Kim, Chul-Hoo Kang, Sung Il Sohn, Jeong-Ho Hong, Seong Hwa Jang, Hyungjong Park, Tai Hwan Park, Sang-Soon Park, Kyung Bok Lee, Jee-Hyun Kwon, Wook-Joo Kim, Jun Lee, Doo Hyuk Kwon, Dong-Seok Gwak, Dong-Eog Kim, Keon-Joo Lee, Sang-Hwa Lee, Chulho Kim, Hae-Bong Jeong, Kwang Yeol Park, Ji Sung Lee, Juneyoung Lee, Nicolas Martinez-Majander, Gerli Sibolt, Marjaana Tiainen, Mauro Gentile, Ludovica Migliaccio, Luigi Simonetti, Matteo Paolucci, Alan Flores, Laia Seró, Guillaume Turc, Catherine Oppenheim, Olivier Naggara, Wagih Ben Hassen, Joseph Benzakoun, Yusuke Yakushiji, Takenobu Kunieda, Georg Kägi, Stefan Engelter, Christian H. Nolte, Bernd Kallmünzer, Patrik Michel, Timothy J. Kleinig, John Fink, Ole Morten Rønning, Bruce Campbell, Paul J. Nederkoorn, Götz Thomalla, Takenobu Kunieda, Khouloud Poli, Yannick Béjot, Yannie Soo, Carlos Garcia-Esperon, Georges Ntaios, Charlotte Cordonnier, João Pedro Marto, Guido Bigliardi, François Lun, Philip M. C. Choi, Thorsten Steiner, Xavier Ustrell, David Werring, Susanne Wegener, Alessandro Pezzini, Houwei Du, Joan Martí-Fàbregas, David Cánovas-Vergé, Daniel Strbian, Visnja Padjen, Shadi Yaghi, Christoph Stretz, Joon-Tae Kim
Journal: JAMA Neurology (2023)

International guidelines recommend avoiding intravenous thrombolysis (IVT) in patients with ischemic stroke who have a recent intake of a direct oral anticoagulant (DOAC). To determine the risk of symptomatic intracranial hemorrhage (sICH) associated with use of IVT in patients with recent DOAC ingestion. This international, multicenter, retrospective cohort study included 64 primary and comprehensive stroke centers across Europe, Asia, Australia, and New Zealand. Consecutive adult patients with ischemic stroke who received IVT (both with and without thrombectomy) were included. Patients whose last known DOAC ingestion was more than 48 hours before stroke onset were excluded. A total of 832 patients with recent DOAC use were compared with 32 375 controls without recent DOAC use. Data were collected from January 2008 to December 2021. Prior DOAC therapy (confirmed last ingestion within 48 hours prior to IVT) compared with no prior oral anticoagulation. The main outcome was sICH within 36 hours after IVT, defined as worsening of at least 4 points on the National Institutes of Health Stroke Scale and attributed to radiologically evident intracranial hemorrhage. Outcomes were compared according to different selection strategies (DOAC-level measurements, DOAC reversal treatment, IVT with neither DOAC-level measurement nor idarucizumab). The association of sICH with DOAC plasma levels and very recent ingestions was explored in sensitivity analyses. Of 33 207 included patients, 14 458 (43.5%) were female, and the median (IQR) age was 73 (62-80) years. The median (IQR) National Institutes of Health Stroke Scale score was 9 (5-16). Of the 832 patients taking DOAC, 252 (30.3%) received DOAC reversal before IVT (all idarucizumab), 225 (27.0%) had DOAC-level measurements, and 355 (42.7%) received IVT without measuring DOAC plasma levels or reversal treatment. The unadjusted rate of sICH was 2.5% (95% CI, 1.6-3.8) in patients taking DOACs compared with 4.1% (95% CI, 3.9-4.4) in control patients using no anticoagulants. Recent DOAC ingestion was associated with lower odds of sICH after IVT compared with no anticoagulation (adjusted odds ratio, 0.57; 95% CI, 0.36-0.92). This finding was consistent among the different selection strategies and in sensitivity analyses of patients with detectable plasma levels or very recent ingestion. In this study, there was insufficient evidence of excess harm associated with off-label IVT in selected patients after ischemic stroke with recent DOAC ingestion.